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    Age-related changes in prefrontal and hippocampal contributions to relational encoding. Addis Donna Rose,Giovanello Kelly S,Vu Mai-Anh,Schacter Daniel L NeuroImage Age-related declines in relational encoding are well documented. It remains unclear, however, whether such declines reflect dysfunction of (1) ventrolateral prefrontal cortex (VLPFC) and deficient generation of associations; and/or (2) hippocampal dysfunction and impoverished binding of associations. In order to separate VLPFC and hippocampal contributions to relational encoding, we manipulated the generative demands of the encoding task by varying the number of semantic associations between the to-be-encoded information (three words). Thus, trials with fewer semantic associations (lower-association trials) require more generative processing during encoding, relative to trials in which more semantic associations are provided for binding (higher-association trials). Parametric modulation analyses on successfully encoded items revealed that, unlike younger adults, older adults did not show an up-regulation of VLPFC activity during lower-association trials. In contrast, hippocampal activity in both older and younger adults was greater in higher- relative to lower-association trials. Moreover, recognition accuracy improved significantly in both groups with the provision of more semantic associations, indicating that both younger and older adults benefitted from this form of encoding support. Our findings suggest that left VLPFC dysfunction may underlie relational encoding deficits in older adults, but that when provided with associations to bind, hippocampal activity in older adults is comparable to young, consistent with their increased recognition accuracy under conditions of encoding support. 10.1016/j.neuroimage.2013.08.033
    Neural Correlates of Associative Memory in the Elderly: A Resting-State Functional MRI Study. Ren Weicong,Li Rui,Zheng Zhiwei,Li Juan BioMed research international The neural correlates of associative memory in healthy older adults were investigated by examining the correlation of associative memory performance with spontaneous brain oscillations. Eighty healthy older adults underwent a resting-state functional MRI and took a paired-associative learning test (PALT). Correlations between the amplitude of low-frequency fluctuations (ALFF) as well as fractional ALFF (fALFF) in the whole brain and PALT scores were calculated. We found that spontaneous activity as indexed by both ALFF and fALFF in the parahippocampal gyrus (PHG) was significantly positively correlated with associative memory performance, suggesting that the PHG plays a critical role in associative memory in older people. 10.1155/2015/129180
    Sex Matters: Hippocampal Volume Predicts Individual Differences in Associative Memory in Cognitively Normal Older Women but Not Men. Zheng Zhiwei,Li Rui,Xiao Fengqiu,He Rongqiao,Zhang Shouzi,Li Juan Frontiers in human neuroscience The hippocampus plays a prominent role in associative memory by supporting relational binding and recollection processes. Structural atrophy in the hippocampus is likely to induce associative memory deficits in older adults. Previous studies have primarily focused on average age-related differences in hippocampal structure and memory performance. To date, however, it remains unclear whether individual differences in hippocampal morphometry underlie differential associative memory performance, and whether there are sex differences in the structural correlates of associative memory in healthy older adults. Here, we used voxel-based morphometry (VBM) to examine the extent to which gray matter volume (GMV) of the hippocampus predicts associative memory performance in cognitively normal older adults. Seventy-one participants completed a cued recall paired-associative learning test (PALT), which consists of novel associations and semantically related associations, and underwent magnetic resonance imaging (MRI). We observed worse associative memory performance and larger variability for novel associations than for semantically related associations. The VBM results revealed that higher scores on associative memory for novel associations were related to greater hippocampal GMV across all older adults. When considering men and women separately, the correlation between hippocampal GMV and associative memory performance for novel associations reached significance only in older women. These findings suggest that hippocampal structural volumes may predict individual differences in novel associative memory in older women but not men. 10.3389/fnhum.2017.00093
    Neural Network Connectivity During Post-encoding Rest: Linking Episodic Memory Encoding and Retrieval. Risius Okka J,Onur Oezguer A,Dronse Julian,von Reutern Boris,Richter Nils,Fink Gereon R,Kukolja Juraj Frontiers in human neuroscience Commonly, a switch between networks mediating memory encoding and those mediating retrieval is observed. This may not only be due to differential involvement of neural resources due to distinct cognitive processes but could also reflect the formation of new memory traces and their dynamic change during consolidation. We used resting state fMRI to measure functional connectivity (FC) changes during post-encoding rest, hypothesizing that during this phase, new functional connections between encoding- and retrieval-related regions are created. Interfering and reminding tasks served as experimental modulators to corroborate that the observed FC differences indeed reflect changes specific to post-encoding rest. The right inferior occipital and fusiform gyri (active during encoding) showed increased FC with the left inferior frontal gyrus and the left middle temporal gyrus (MTG) during post-encoding rest. Importantly, the left MTG subsequently also mediated successful retrieval. This finding might reflect the formation of functional connections between encoding- and retrieval-related regions during undisturbed post-encoding rest. These connections were vulnerable to experimental modulation: Cognitive interference disrupted FC changes during post-encoding rest resulting in poorer memory performance. The presentation of reminders also inhibited FC increases but without affecting memory performance. Our results contribute to a better understanding of the mechanisms by which post-encoding rest bridges the gap between encoding- and retrieval-related networks. 10.3389/fnhum.2018.00528
    Auditory and Visual Tasks Influence the Temporal Dynamics of EEG Microstates During Post-encoding Rest. D'Croz-Baron David F,Bréchet Lucie,Baker Mary,Karp Tanja Brain topography Re-activations of task-dependent patterns of neural activity take place during post-encoding periods of wakeful rest and sleep. However, it is still unclear how the temporal dynamics of brain states change during these periods, which are shaped by prior conscious experiences. Here, we examined the very brief periods of wakeful rest immediately after encoding and recognition of auditory and visual stimuli, by applying the EEG microstate analysis, in which the global variance of the EEG is explained by only a few prototypical topographies. We identified the dominant brain states of sub-second duration during the tasks-dependent periods of rest, finding that the temporal dynamics-represented here by two temporal parameters: the frequency of occurrence and the fraction of time coverage-of three task-related microstate classes changed compared to wakeful rest. This study provides evidence of experience-dependent temporal changes in post-encoding periods of resting brain activity, which can be captured using the EEG microstates approach. 10.1007/s10548-020-00802-4
    Increased resting-state perfusion after repeated encoding is related to later retrieval of declarative associative memories. Groen Georg,Sokolov Alexander N,Jonas Christina,Roebling Robert,Spitzer Manfred PloS one Electrophysiological studies in animals have shown coordinated reactivation of neuronal ensembles during a restricted time period of behavioral inactivity that immediately followed active encoding. In the present study we directly investigated off-line processing of associative memory formation in the human brain. Subjects' regional cerebral blood flow (rCBF) as a surrogate marker of neural activity during rest was measured by MR-based perfusion imaging in a sample of 14 healthy male subjects prior to (Pre2) and after (Post) extensive learning of 24 face-name associations within a selective reminding task (SR). Results demonstrated significant Post-Pre2 rCBF increases in hippocampal and temporal lobe regions, while in a control comparison of two perfusion scans with no learning task in-between (Pre2-Pre1) no differences in rCBF emerged. Post perfusion scanning was followed by a surprise cued associative recall task from which two types of correctly retrieved names were obtained: older names already correctly retrieved at least once during one of the SR blocks, and recent names acquired during the last SR block immediately prior to the Post scan. In the anterior hippocampus individual perfusion increases were correlated with both correct retrievals of older and recent names. By contrast, older but not recently learned names showed a significant correlation with perfusion increases in the left lateral temporal cortex known to be associated with long-term memory. Recent, but not older names were correlated with dopaminergic midbrain structures reported to contribute to the persistence of memory traces for novel information. Although the direct investigation of off-line memory processing did not permit concomitant experimental control, neither intentional rehearsal, nor substantial variations in subjects' states of alertness appear to contribute to present results. We suggest that the observed rCBF increases might reflect processes that possibly contribute to the long-term persistence of memory traces. 10.1371/journal.pone.0019985
    Benefit of wakeful resting on gist and peripheral memory retrieval in healthy younger and older adults. Sacripante Riccardo,McIntosh Robert D,Della Sala Sergio Neuroscience letters Retrieval is greater if new learning is followed by a period of wakeful rest, minimising the likelihood of retroactive interference. It is not known if this benefit extends to recollection of both gist and peripheral details, nor whether age affects the benefit of wakeful resting in either of these types of recollection. Forty-five younger and forty older adults were presented with prose passages for later recall followed by a period of either interference or wakeful resting. Younger participants outperformed older participants in remembering peripheral details, but not on gist memory. Wakeful resting led to higher overall recollection in both age groups, both for gist and for peripheral details. Also, wakeful resting was more beneficial for gist than peripheral memory in older but not younger adults. We discuss these novel findings and their theoretical implications for a memory consolidation account of the benefits of wakeful resting. 10.1016/j.neulet.2019.04.026
    The Efficiency of Online "Inked" Videos Versus Recorded PowerPoint Lectures on Teaching Pathophysiology to Medical Students in Pre-Clerkship Years: A Pilot Study. Journal of medical education and curricular development BACKGROUND:As online learning develops an increasingly important role in medical education, new online teaching modalities are arising all the time. One such teaching modality that is gaining popularity among medical students is the "inked" video, a type of animated video that utilizes a virtual blackboard. Student reviews suggest that the dynamic style of the inked video allows it to teach more efficiently than traditional teaching modalities, but currently there is no quantitative evidence to support or guide the use of this teaching modality. HYPOTHESIS:When compared to the traditional recorded PowerPoint lecture, online inked videos teach the same pathophysiology concepts to pre-clerkship medical students in a shorter amount of time. METHOD:A randomized, crossover-design study was conducted with second-year medical students at the David Geffen School of Medicine at University of California, Los Angeles (n = 22). Students were randomized to 2 groups. Each group received 2 lessons on 2 different pathophysiology topics: one via a shorter inked video and the other via a longer recorded PowerPoint lecture. Two sets of dependent variables were used to test modality effects: immediate post-tests scores and delayed retention post-test scores. A perceptions survey was also administered to assess student preferences between the 2 teaching modalities. RESULTS:Students performed similarly on immediate and delayed post-tests for the shorter inked videos and the longer recorded PowerPoint lectures ( > .05). Students reported greater engagement ( < .05) and greater satisfaction with learning ( < .05) with the inked videos than the recorded PowerPoint lectures. CONCLUSIONS:This study, although limited by its small-scale and single-institution design, provides preliminary evidence that online inked videos may be a more efficient and non-inferior alternative to recorded PowerPoint lectures. 10.1177/2382120519897031
    Dissociable neural mechanisms for goal-directed versus incidental memory reactivation. Kuhl Brice A,Johnson Marcia K,Chun Marvin M The Journal of neuroscience : the official journal of the Society for Neuroscience Remembering a past event involves reactivation of distributed patterns of neural activity that represent the features of that event-a process that depends on associative mechanisms supported by medial temporal lobe structures. Although efficient use of memory requires prioritizing those features of a memory that are relevant to current behavioral goals (target features) over features that may be goal-irrelevant (incidental features), there remains ambiguity concerning how this is achieved. We tested the hypothesis that although medial temporal lobe structures may support reactivation of both target and incidental event features, frontoparietal cortex preferentially reactivates those features that match current goals. Here, human participants were cued to remember either the category (face/scene) to which a picture belonged (category trials) or the location (left/right) in which a picture appeared (location trials). Multivoxel pattern analysis of fMRI data were used to measure reactivation of category information as a function of its behavioral relevance (target vs incidental reactivation). In ventral/medial temporal lobe (VMTL) structures, incidental reactivation was as robust as target reactivation. In contrast, frontoparietal cortex exhibited stronger target than incidental reactivation; that is, goal-modulated reactivation. Reactivation was also associated with later memory. Frontoparietal biases toward target reactivation predicted subsequent memory for target features, whereas incidental reactivation in VMTL predicted subsequent memory for nontested features. These findings reveal a striking dissociation between goal-modulated reactivation in frontoparietal cortex and incidental reactivation in VMTL. 10.1523/JNEUROSCI.0207-13.2013
    Recollection-related increases in functional connectivity predict individual differences in memory accuracy. King Danielle R,de Chastelaine Marianne,Elward Rachael L,Wang Tracy H,Rugg Michael D The Journal of neuroscience : the official journal of the Society for Neuroscience Recollection involves retrieving specific contextual details about a prior event. Functional neuroimaging studies have identified several brain regions that are consistently more active during successful versus failed recollection-the "core recollection network." In the present study, we investigated whether these regions demonstrate recollection-related increases not only in activity but also in functional connectivity in healthy human adults. We used fMRI to compare time-series correlations during successful versus unsuccessful recollection in three separate experiments, each using a different operational definition of recollection. Across experiments, a broadly distributed set of regions consistently exhibited recollection-related increases in connectivity with different members of the core recollection network. Regions that demonstrated this effect included both recollection-sensitive regions and areas where activity did not vary as a function of recollection success. In addition, in all three experiments the magnitude of connectivity increases correlated across individuals with recollection accuracy in areas diffusely distributed throughout the brain. These findings suggest that enhanced functional interactions between distributed brain regions are a signature of successful recollection. In addition, these findings demonstrate that examining dynamic modulations in functional connectivity during episodic retrieval will likely provide valuable insight into neural mechanisms underlying individual differences in memory performance. 10.1523/JNEUROSCI.3219-14.2015
    Distributed learning enhances relational memory consolidation. Litman Leib,Davachi Lila Learning & memory (Cold Spring Harbor, N.Y.) It has long been known that distributed learning (DL) provides a mnemonic advantage over massed learning (ML). However, the underlying mechanisms that drive this robust mnemonic effect remain largely unknown. In two experiments, we show that DL across a 24 hr interval does not enhance immediate memory performance but instead slows the rate of forgetting relative to ML. Furthermore, we demonstrate that this savings in forgetting is specific to relational, but not item, memory. In the context of extant theories and knowledge of memory consolidation, these results suggest that an important mechanism underlying the mnemonic benefit of DL is enhanced memory consolidation. We speculate that synaptic strengthening mechanisms supporting long-term memory consolidation may be differentially mediated by the spacing of memory reactivation. These findings have broad implications for the scientific study of episodic memory consolidation and, more generally, for educational curriculum development and policy. 10.1101/lm.1132008
    Acute Exercise on Memory Reconsolidation. Loprinzi Paul D,Lovorn Ashley,Hamilton Emma,Mincarelli Noelle Journal of clinical medicine BACKGROUND AND OBJECTIVE:Once a memory is reactivated, it enters a labile state and, thus, is vulnerable to memory decay and/or distortion. Recent research demonstrates that acute, high-intensity exercise is associated with enhanced episodic memory function. Very limited research, however, has evaluated whether acute exercise can attenuate memory distortion from memory reactivation, which was the purpose of this study. METHODS:A between-subject randomized controlled intervention was employed. Participants (N = 80) were randomly assigned to one of four groups, including (1) reminder with exercise, (2) reminder, (3) no reminder, and (4) interference control. For the groups, participants completed three visits (Visit 1, 2, and 3), which all occurred 48 hours apart. An exception to this was the interference control group, which did not complete Visit 2. On Visit 2, the reminder with exercise group engaged in a 15 min bout of high-intensity exercise (80% of heart rate reserve) immediately after memory reactivation. On Visit 3, participants engaged in a free recall (4 trials) of the memory task encoded on Visit 1. RESULTS:In a 4 (groups) × 4 (learning trials) mixed-measures ANOVA, with the group as the between-subjects variable and the learning trials (1-4) as the within-subject variable, there was a significant main effect group, (3, 76) = 4.18, = 0.008, η = 0.14, and a significant main effect for the learning trials, (2.40, 182.59) = 49.25, < 0.001, η = 0.39, but there was no group by learning trials interaction, (7.20, 182.59) = 1.07, = 0.38, η = 0.04. CONCLUSION:Our findings suggest that exercise may, potentially, attenuate memory distortion from memory reactivation. However, future work is needed to confirm these findings before any strong conclusions can be reached. 10.3390/jcm8081200
    Resting States and Memory Consolidation: A Preregistered Replication and Meta-Analysis. Humiston Graelyn B,Tucker Matthew A,Summer Theodore,Wamsley Erin J Scientific reports While several recent studies have found that a post-encoding period of quiet, eyes-closed waking rest benefits memory consolidation, others have reported null effects. To more precisely estimate this effect, we conducted a quasi-exact behavioural replication of a recent study from our lab, which found that post-training eyes-closed waking rest improved declarative memory relative to a distractor task. Contrary to our hypothesis, the observed effect was not significant; however, it did fall within the 95% confidence interval of our previous finding. Furthermore, a meta-analytic effect summarizing n = 10 similar studies indicates a moderately sized and significant benefit of waking rest for verbal memory (d = 0.38, p < 0.001). We argue that the apparently conflicting results in this literature are most parsimoniously explained by variability due to sampling and/or measurement error, in a group of studies often underpowered to detect a smaller-than-expected effect of rest. Additionally, exploratory analyses revealed that increased trait daydreaming frequency negatively correlated with memory retention during eyes-closed rest. Together with our replication and meta-analysis, these studies suggest that waking rest confers a small but significant benefit on memory consolidation, and that this benefit requires the mind to be free from attention to either external tasks or spontaneous thought. 10.1038/s41598-019-56033-6
    Resting-state networks of the neonate brain identified using independent component analysis. Rajasilta Olli,Tuulari Jetro J,Björnsdotter Malin,Scheinin Noora M,Lehtola Satu J,Saunavaara Jani,Häkkinen Suvi,Merisaari Harri,Parkkola Riitta,Lähdesmäki Tuire,Karlsson Linnea,Karlsson Hasse Developmental neurobiology Resting-state functional magnetic resonance imaging (rs-fMRI) has been successfully used to probe the intrinsic functional organization of the brain and to study brain development. Here, we implemented a combination of individual and group independent component analysis (ICA) of FSL on a 6-min resting-state data set acquired from 21 naturally sleeping term-born (age 26 ± 6.7 d), healthy neonates to investigate the emerging functional resting-state networks (RSNs). In line with the previous literature, we found evidence of sensorimotor, auditory/language, visual, cerebellar, thalmic, parietal, prefrontal, anterior cingulate as well as dorsal and ventral aspects of the default-mode-network. Additionally, we identified RSNs in frontal, parietal, and temporal regions that have not been previously described in this age group and correspond to the canonical RSNs established in adults. Importantly, we found that careful ICA-based denoising of fMRI data increased the number of networks identified with group-ICA, whereas the degree of spatial smoothing did not change the number of identified networks. Our results show that the infant brain has an established set of RSNs soon after birth. 10.1002/dneu.22742
    The resting human brain and motor learning. Albert Neil B,Robertson Edwin M,Miall R Chris Current biology : CB Functionally related brain networks are engaged even in the absence of an overt behavior. The role of this resting state activity, evident as low-frequency fluctuations of BOLD (see [1] for review, [2-4]) or electrical [5, 6] signals, is unclear. Two major proposals are that resting state activity supports introspective thought or supports responses to future events [7]. An alternative perspective is that the resting brain actively and selectively processes previous experiences [8]. Here we show that motor learning can modulate subsequent activity within resting networks. BOLD signal was recorded during rest periods before and after an 11 min visuomotor training session. Motor learning but not motor performance modulated a fronto-parietal resting state network (RSN). Along with the fronto-parietal network, a cerebellar network not previously reported as an RSN was also specifically altered by learning. Both of these networks are engaged during learning of similar visuomotor tasks [9-22]. Thus, we provide the first description of the modulation of specific RSNs by prior learning--but not by prior performance--revealing a novel connection between the neuroplastic mechanisms of learning and resting state activity. Our approach may provide a powerful tool for exploration of the systems involved in memory consolidation. 10.1016/j.cub.2009.04.028
    Persistent schema-dependent hippocampal-neocortical connectivity during memory encoding and postencoding rest in humans. van Kesteren Marlieke T R,Fernández Guillén,Norris David G,Hermans Erno J Proceedings of the National Academy of Sciences of the United States of America The hippocampus is thought to promote gradual incorporation of novel information into long-term memory by binding, reactivating, and strengthening distributed cortical-cortical connections. Recent studies implicate a key role in this process for hippocampally driven crosstalk with the (ventro)medial prefrontal cortex (vmPFC), which is proposed to become a central node in such representational networks over time. The existence of a relevant prior associative network, or schema, may moreover facilitate this process. Thus, hippocampal-vmPFC crosstalk may support integration of new memories, particularly in the absence of a relevant prior schema. To address this issue, we used functional magnetic resonance imaging (fMRI) and prior schema manipulation to track hippocampal-vmPFC connectivity during encoding and postencoding rest. We manipulated prior schema knowledge by exposing 30 participants to the first part of a movie that was temporally scrambled for 15 participants. The next day, participants underwent fMRI while encoding the movie's final 15 min in original order and, subsequently, while resting. Schema knowledge and item recognition performance show that prior schema was successfully and selectively manipulated. Intersubject synchronization (ISS) and interregional partial correlation analyses furthermore show that stronger prior schema was associated with more vmPFC ISS and less hippocampal-vmPFC interregional connectivity during encoding. Notably, this connectivity pattern persisted during postencoding rest. These findings suggest that additional crosstalk between hippocampus and vmPFC is required to compensate for difficulty integrating novel information during encoding and provide tentative support for the notion that functionally relevant hippocampal-neocortical crosstalk persists during off-line periods after learning. 10.1073/pnas.0914892107
    The slow forgetting of emotional episodic memories: an emotional binding account. Yonelinas Andrew P,Ritchey Maureen Trends in cognitive sciences Emotional events are remembered better than neutral events, and this emotion advantage becomes particularly pronounced over time. The time-dependent effects of emotion impact upon recollection rather than on familiarity-based recognition, and they influence the recollection of item-specific details rather than contextual details. Moreover, the amygdala, but not the hippocampus, is crucial for producing these effects. Time-dependent effects of emotion have been attributed to an emotional consolidation process whereby the amygdala gradually facilitates the storage of emotional memories by other medial temporal lobe regions. However, we propose that these effects can be better understood by an emotional binding account whereby the amygdala mediates the recollection of item-emotion bindings that are forgotten more slowly than item-context bindings supported by the hippocampus. 10.1016/j.tics.2015.02.009
    Resting-state functional connectivity MRI reveals active processes central to cognition. Stevens W Dale,Spreng R Nathan Wiley interdisciplinary reviews. Cognitive science Analysis of spontaneously correlated low-frequency activity fluctuations across the brain using functional magnetic resonance imaging (MRI)-commonly referred to as resting-state functional connectivity (RSFC) MRI-was initially seen as a useful tool for mapping functional-anatomic networks in the living human brain, characterizing brain changes and differences in clinical populations, and studying comparative anatomy across species. However, little was known about the potential relevance of RSFC to cognitive processes. Indeed, there has been considerable controversy and debate as to the utility of studying the resting-state in cognitive neuroscience. However, recent work has shown that RSFC, rather than merely reflecting passive or epiphenomenal activity within underlying functional-anatomic networks, reveals important dynamic processes that play an active role in cognition. RSFC has been associated with individual differences in a number of behavioral and cognitive domains, including perception, language, learning and memory, and the organization of conceptual knowledge. In this article, we review and integrate the latest research demonstrating that RSFC is functionally relevant to human behavior and higher-level cognition, and propose a hypothesis regarding its mechanism of action on functional network dynamics and cognition. We conclude that RSFC MRI will be an invaluable tool for future discovery of the fundamental neurocognitive interactions that underlie cognition. WIREs Cogn Sci 2014, 5:233-245. doi: 10.1002/wcs.1275 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. 10.1002/wcs.1275
    Post-Encoding Amygdala-Visuosensory Coupling Is Associated with Negative Memory Bias in Healthy Young Adults. Kark Sarah M,Kensinger Elizabeth A The Journal of neuroscience : the official journal of the Society for Neuroscience The amygdala is well documented as the critical nexus of emotionally enhanced memory, yet its role in the creation of negative memory biases, better memory for negative compared with positive stimuli, has not been clarified. Although prior work suggests valence-specific effects at the moment of "online" encoding and retrieval, with enhanced visuosensory processes supporting negative memories in particular, here we tested the novel hypothesis that the amygdala engages with distant cortical regions after encoding in a manner that predicts inter-individual differences in negative memory biases in humans. Twenty-nine young adults (males and females) were scanned while they incidentally encoded negative, neutral, and positive scenes, each preceded by a line-drawing sketch of the scene. Twenty-four hours later, participants were scanned during an Old/New recognition memory task with only the line-drawings presented as retrieval cues. We replicated and extended our prior work, showing that enhanced online visuosensory recapitulation supports negative memory. Critically, resting-state scans flanked the encoding task, allowing us to show for the first time that individual differences in "off-line" increases in amygdala resting-state functional connectivity (RSFC) immediately following encoding relate to negative and positive memory bias at test. Specifically, post-encoding increases in amygdala RSFC with visuosensory and frontal regions were associated with the degree of negative and positive memory bias, respectively. These findings provide new evidence that valence-specific negative memory biases can be linked to the way that sensory processes are integrated into amygdala-centered emotional memory networks. Decades of research has placed the amygdala at the center of the emotional memory network. Despite the clinical importance of disproportionate memory for negative compared with positive events, it is not known whether post-encoding increases in amygdala-cortical coupling, possibly reflective of early consolidation processes, bear any influence on the degree or direction of such emotional memory biases. We demonstrate that, across participants, increases in post-encoding amygdala coupling with visuosensory and frontal regions are associated with more pronounced negative and positive memory biases, respectively. These findings provide the first evidence linking post-encoding amygdala modulation to the degree of negative or positive memory bias, emphasizing the need for valence-based accounts of the amygdala's role in emotional memory. 10.1523/JNEUROSCI.2834-18.2019
    Thalamo-cortical coupling during encoding and consolidation is linked to durable memory formation. Wagner Isabella C,van Buuren Mariët,Fernández Guillén NeuroImage Memory formation transforms experiences into durable engrams. The stabilization critically depends on processes during and after learning, and involves hippocampal-medial prefrontal interactions that appear to be mediated by the nucleus reuniens of the thalamus in rodents, which corresponds to the human medioventral thalamus. How this region contributes to durable memory formation in humans is, however, unclear. Furthermore, the anterior-, lateral dorsal-, and mediodorsal nuclei appear to promote mnemonic function as well. We hypothesized that durable memory formation is associated with increases in thalamo-cortical interactions during encoding and consolidation. Thirty-three human subjects underwent fMRI while studying picture-location associations. To assess consolidation, resting-state brain activity was measured after study and was compared to a pre-study baseline. Memory was tested on the same day and 48 h later. While "weak" memories could only be remembered at the immediate test, "durable" memories persisted also after the delay. We found increased coupling of the medioventral-, adjacent anterior-, lateral dorsal-, and mediodorsal thalamus with the hippocampus and surrounding medial temporal lobe, as well as with anterior and posterior midline regions related to durable memory encoding. The medioventral and lateral dorsal thalamus showed increased connectivity with posterior medial and parietal cortex from baseline to post-encoding rest, positively scaling with the proportion of durable memories formed across subjects. Additionally, the lateral dorsal thalamus revealed consolidation-related coupling with the inferior temporal, retrosplenial, and medial prefrontal cortex. We suggest that thalamo-cortical cross-talk strengthens mnemonic representations at initial encoding, and that cortical coupling of specific thalamic subregions supports consolidation thereafter. 10.1016/j.neuroimage.2019.04.055
    Intrinsic spontaneous brain activity predicts individual variability in associative memory in older adults. Zheng Zhiwei,Li Rui,Xiao Fengqiu,He Rongqiao,Zhang Shouzi,Li Juan PsyCh journal Older adults demonstrate notable individual differences in associative memory. Here, resting-state functional magnetic resonance imaging (rsfMRI) was used to investigate whether intrinsic brain activity at rest could predict individual differences in associative memory among cognitively healthy older adults. Regional amplitude of low-frequency fluctuations (ALFF) analysis and a correlation-based resting-state functional connectivity (RSFC) approach were used to analyze data acquired from 102 cognitively normal elderly who completed the paired-associative learning test (PALT) and underwent fMRI scans. Participants were divided into two groups based on the retrospective self-reports on whether or not they utilized encoding strategies during the PALT. The behavioral results revealed better associative memory performance in the participants who reported utilizing memory strategies compared with participants who reported not doing so. The fMRI results showed that higher associative memory performance was associated with greater functional connectivity between the right superior frontal gyrus and the right posterior cerebellum lobe in the strategy group. The regional ALFF values in the right superior frontal gyrus were linked to associative memory performance in the no-strategy group. These findings suggest that the regional spontaneous fluctuations and functional connectivity during rest may subserve the individual differences in the associative memory in older adults, and that this is modulated by self-initiated memory strategy use. 10.1002/pchj.212
    Electrophysiological mechanisms of human memory consolidation. Zhang Hui,Fell Juergen,Axmacher Nikolai Nature communications Consolidation stabilizes memory traces after initial encoding. Rodent studies suggest that memory consolidation depends on replay of stimulus-specific activity patterns during fast hippocampal "ripple" oscillations. Here, we measured replay in intracranial electroencephalography recordings in human epilepsy patients, and related replay to ripples. Stimulus-specific activity was identified using representational similarity analysis and then tracked during waking rest and sleep after encoding. Stimulus-specific gamma (30-90 Hz) activity during early (100-500 ms) and late (500-1200 ms) encoding is spontaneously reactivated during waking state and sleep, independent of later memory. Ripples during nREM sleep, but not during waking state, trigger replay of activity from the late time window specifically for remembered items. Ripple-triggered replay of activity from the early time window during nREM sleep is enhanced for forgotten items. These results provide the first electrophysiological evidence for replay related to memory consolidation in humans, and point to a prominent role of nREM ripple-triggered replay in consolidation processes. 10.1038/s41467-018-06553-y
    Brief targeted memory reactivation during the awake state enhances memory stability and benefits the weakest memories. Tambini Arielle,Berners-Lee Alice,Davachi Lila Scientific reports Reactivation of representations corresponding to recent experience is thought to be a critical mechanism supporting long-term memory stabilization. Targeted memory reactivation, or the re-exposure of recently learned cues, seeks to induce reactivation and has been shown to benefit later memory when it takes place during sleep. However, despite recent evidence for endogenous reactivation during post-encoding awake periods, less work has addressed whether awake targeted memory reactivation modulates memory. Here, we found that brief (50 ms) visual stimulus re-exposure during a repetitive foil task enhanced the stability of cued versus uncued associations in memory. The extent of external or task-oriented attention prior to re-exposure was inversely related to cueing benefits, suggesting that an internally-orientated state may be most permissible to reactivation. Critically, cueing-related memory benefits were greatest in participants without explicit recognition of cued items and remained reliable when only considering associations not recognized as cued, suggesting that explicit cue-triggered retrieval processes did not drive cueing benefits. Cueing benefits were strongest for associations and participants with the poorest initial learning. These findings expand our knowledge of the conditions under which targeted memory reactivation can benefit memory, and in doing so, support the notion that reactivation during awake time periods improves memory stabilization. 10.1038/s41598-017-15608-x
    Comparing the Effects of Sleep and Rest on Memory Consolidation. Nature and science of sleep INTRODUCTION:There is ample evidence that overnight sleep and daytime naps benefit memory retention, compared to comparable amounts of active wakefulness. Yet recent evidence also suggests that a period of post-training rest (eg, quiet wakefulness with eyes closed) provides a similar memory benefit compared to wake. However, the relative benefits of sleep vs quiet waking rest on memory remain poorly understood. Here, we assessed the extent to which sleep provides a unique memory benefit, above and beyond that conferred by quiet waking rest. METHODS:In a sample of healthy undergraduate students (N=83), we tested the effect of 30 mins of post-learning sleep, rest, or active wake on concept learning (dot pattern classification) and declarative memory (word pair associates) across a 4-hr daytime training-retest interval. RESULTS AND CONCLUSIONS:Contrary to our hypotheses, we found no differences in performance between the three conditions for either task. The findings are interpreted with reference to methodological considerations including the length of the experimental interval, the nature of the tasks used, and challenges inherent in creating experimental conditions that can be executed by participants. 10.2147/NSS.S223917
    Increased Hippocampus-Medial Prefrontal Cortex Resting-State Functional Connectivity and Memory Function after Tai Chi Chuan Practice in Elder Adults. Tao Jing,Liu Jiao,Egorova Natalia,Chen Xiangli,Sun Sharon,Xue Xiehua,Huang Jia,Zheng Guohua,Wang Qin,Chen Lidian,Kong Jian Frontiers in aging neuroscience Previous studies provide evidence that aging is associated with the decline of memory function and alterations in the hippocampal (HPC) function, including functional connectivity to the medial prefrontal cortex (mPFC). In this study, we investigated if longitudinal (12-week) Tai Chi Chuan and Baduanjin practice can improve memory function and modulate HPC resting-state functional connectivity (rs-FC). Memory function measurements and resting-state functional magnetic resonance imaging (rs-fMRI) were applied at the beginning and the end of the experiment. The results showed that (1) the memory quotient (MQ) measured by the Wechsler Memory Scale-Chinese Revision significantly increased after Tai Chi Chuan and Baduanjin practice as compared with the control group, and no significant difference was observed in MQ between the Tai Chi Chuan and Baduanjin groups; (2) rs-FC between the bilateral hippocampus and mPFC significantly increased in the Tai Chi Chuan group compared to the control group (also in the Baduanjin group compared to the control group, albeit at a lower threshold), and no significant difference between the Tai Chi Chuan and Baduanjin groups was observed; (3) rs-FC increases between the bilateral hippocampus and mPFC were significantly associated with corresponding memory function improvement across all subjects. Similar results were observed using the left or right hippocampus as seeds. Our results suggest that both Tai Chi Chuan and Baduanjin may be effective exercises to prevent memory decline during aging. 10.3389/fnagi.2016.00025
    DAF-16 target genes that control C. elegans life-span and metabolism. Lee Siu Sylvia,Kennedy Scott,Tolonen Andrew C,Ruvkun Gary Science (New York, N.Y.) Signaling from the DAF-2/insulin receptor to the DAF-16/FOXO transcription factor controls longevity, metabolism, and development in disparate phyla. To identify genes that mediate the conserved biological outputs of daf-2/insulin-like signaling, we used comparative genomics to identify 17 orthologous genes from Caenorhabditis and Drosophila, each of which bears a DAF-16 binding site in the promoter region. One-third of these DAF-16 downstream candidate genes were regulated by daf-2/insulin-like signaling in C. elegans, and RNA interference inactivation of the candidates showed that many of these genes mediate distinct aspects of daf-16 function, including longevity, metabolism, and development. 10.1126/science.1083614
    Enhanced brain correlations during rest are related to memory for recent experiences. Tambini Arielle,Ketz Nicholas,Davachi Lila Neuron Long-term storage of episodic memories is hypothesized to result from the off-line transfer of information from the hippocampus to neocortex, allowing a hippocampal-independent cortical representation to emerge. However, off-line hippocampal-cortical interactions have not been demonstrated to be linked with long-term memory. Here, using functional magnetic resonance imaging, we examined if hippocampal-cortical BOLD correlations during rest following an associative encoding task are related to later associative memory performance. Our data show enhanced functional connectivity between the hippocampus and a portion of the lateral occipital complex (LO) during rest following a task with high subsequent memory compared to pretask baseline resting connectivity. This effect is not seen during rest following a task with poor subsequent memory. Furthermore, the magnitude of hippocampal-LO correlations during posttask rest predicts individual differences in later associative memory. These results demonstrate the importance of postexperience resting brain correlations for memory for recent experiences. 10.1016/j.neuron.2010.01.001
    Functional connectivity relationships predict similarities in task activation and pattern information during associative memory encoding. Ritchey Maureen,Yonelinas Andrew P,Ranganath Charan Journal of cognitive neuroscience Neural systems may be characterized by measuring functional interactions in the healthy brain, but it is unclear whether components of systems defined in this way share functional properties. For instance, within the medial temporal lobes (MTL), different subregions show different patterns of cortical connectivity. It is unknown, however, whether these intrinsic connections predict similarities in how these regions respond during memory encoding. Here, we defined brain networks using resting state functional connectivity (RSFC) then quantified the functional similarity of regions within each network during an associative memory encoding task. Results showed that anterior MTL regions affiliated with a network of anterior temporal cortical regions, whereas posterior MTL regions affiliated with a network of posterior medial cortical regions. Importantly, these connectivity relationships also predicted similarities among regions during the associative memory task. Both in terms of task-evoked activation and trial-specific information carried in multivoxel patterns, regions within each network were more similar to one another than were regions in different networks. These findings suggest that functional heterogeneity among MTL subregions may be related to their participation in distinct large-scale cortical systems involved in memory. At a more general level, the results suggest that components of neural systems defined on the basis of RSFC share similar functional properties in terms of recruitment during cognitive tasks and information carried in voxel patterns. 10.1162/jocn_a_00533
    Strengthening connections: functional connectivity and brain plasticity. Kelly Clare,Castellanos F Xavier Neuropsychology review The ascendancy of functional neuroimaging has facilitated the addition of network-based approaches to the neuropsychologist's toolbox for evaluating the sequelae of brain insult. In particular, intrinsic functional connectivity (iFC) mapping of resting state fMRI (R-fMRI) data constitutes an ideal approach to measuring macro-scale networks in the human brain. Beyond the value of iFC mapping for charting how the functional topography of the brain is altered by insult and injury, iFC analyses can provide insights into experience-dependent plasticity at the macro level of large-scale functional networks. Such insights are foundational to the design of training and remediation interventions that will best facilitate recovery of function. In this review, we consider what is currently known about the origin and function of iFC in the brain, and how this knowledge is informative in neuropsychological settings. We then summarize studies that have examined experience-driven plasticity of iFC in healthy control participants, and frame these findings in terms of a schema that may aid in the interpretation of results and the generation of hypotheses for rehabilitative studies. Finally, we outline some caveats to the R-fMRI approach, as well as some current developments that are likely to bolster the utility of the iFC paradigm for neuropsychology. 10.1007/s11065-014-9252-y
    Targeted enhancement of cortical-hippocampal brain networks and associative memory. Wang Jane X,Rogers Lynn M,Gross Evan Z,Ryals Anthony J,Dokucu Mehmet E,Brandstatt Kelly L,Hermiller Molly S,Voss Joel L Science (New York, N.Y.) The influential notion that the hippocampus supports associative memory by interacting with functionally distinct and distributed brain regions has not been directly tested in humans. We therefore used targeted noninvasive electromagnetic stimulation to modulate human cortical-hippocampal networks and tested effects of this manipulation on memory. Multiple-session stimulation increased functional connectivity among distributed cortical-hippocampal network regions and concomitantly improved associative memory performance. These alterations involved localized long-term plasticity because increases were highly selective to the targeted brain regions, and enhancements of connectivity and associative memory persisted for ~24 hours after stimulation. Targeted cortical-hippocampal networks can thus be enhanced noninvasively, demonstrating their role in associative memory. 10.1126/science.1252900
    Intensity-based masking: A tool to improve functional connectivity results of resting-state fMRI. Peer Michael,Abboud Sami,Hertz Uri,Amedi Amir,Arzy Shahar Human brain mapping Seed-based functional connectivity (FC) of resting-state functional MRI data is a widely used methodology, enabling the identification of functional brain networks in health and disease. Based on signal correlations across the brain, FC measures are highly sensitive to noise. A somewhat neglected source of noise is the fMRI signal attenuation found in cortical regions in close vicinity to sinuses and air cavities, mainly in the orbitofrontal, anterior frontal and inferior temporal cortices. BOLD signal recorded at these regions suffers from dropout due to susceptibility artifacts, resulting in an attenuated signal with reduced signal-to-noise ratio in as many as 10% of cortical voxels. Nevertheless, signal attenuation is largely overlooked during FC analysis. Here we first demonstrate that signal attenuation can significantly influence FC measures by introducing false functional correlations and diminishing existing correlations between brain regions. We then propose a method for the detection and removal of the attenuated signal ("intensity-based masking") by fitting a Gaussian-based model to the signal intensity distribution and calculating an intensity threshold tailored per subject. Finally, we apply our method on real-world data, showing that it diminishes false correlations caused by signal dropout, and significantly improves the ability to detect functional networks in single subjects. Furthermore, we show that our method increases inter-subject similarity in FC, enabling reliable distinction of different functional networks. We propose to include the intensity-based masking method as a common practice in the pre-processing of seed-based functional connectivity analysis, and provide software tools for the computation of intensity-based masks on fMRI data. Hum Brain Mapp 37:2407-2418, 2016. © 2016 Wiley Periodicals, Inc. 10.1002/hbm.23182
    Emotional brain states carry over and enhance future memory formation. Tambini Arielle,Rimmele Ulrike,Phelps Elizabeth A,Davachi Lila Nature neuroscience Emotional arousal can produce lasting, vivid memories for emotional experiences, but little is known about whether emotion can prospectively enhance memory formation for temporally distant information. One mechanism that may support prospective memory enhancements is the carry-over of emotional brain states that influence subsequent neutral experiences. Here we found that neutral stimuli encountered by human subjects 9-33 min after exposure to emotionally arousing stimuli had greater levels of recollection during delayed memory testing compared to those studied before emotional and after neutral stimulus exposure. Moreover, multiple measures of emotion-related brain activity showed evidence of reinstatement during subsequent periods of neutral stimulus encoding. Both slow neural fluctuations (low-frequency connectivity) and transient, stimulus-evoked activity predictive of trial-by-trial memory formation present during emotional encoding were reinstated during subsequent neutral encoding. These results indicate that neural measures of an emotional experience can persist in time and bias how new, unrelated information is encoded and recollected. 10.1038/nn.4468
    10 for 10! Cosma Christine,Hinson Ella,Goyal Lakshmi Cell host & microbe 10.1016/j.chom.2017.07.015
    Cortical-hippocampal functional connectivity during covert consolidation sub-serves associative learning: Evidence for an active "rest" state. Ravishankar Mathura,Morris Alexandra,Burgess Ashley,Khatib Dalal,Stanley Jeffrey A,Diwadkar Vaibhav A Brain and cognition We studied modulation of undirected functional connectivity (uFC) in cortical-hippocampal sub-networks during associative learning. Nineteen healthy individuals were studied (fMRI acquired on a Siemens Verio 3T), and uFC was studied between nodes in a network of regions identified by standard activation models based on bivariate correlational analyses of time series data. The paradigm alternated between Memory Encoding, Rest and Retrieval. "Rest" intervals promoted covert consolidation. Over the task, performance was broadly separable into linear (Early) and asymptomatic (Late) regimes, with late performance reflecting successful memory consolidation. Significant modulation of uFC was observed during periods of covert consolidation. The sub-networks which were modulated constituted connections between frontal regions such as the dorsal prefrontal cortex (dPFC) and dorsal anterior cingulate cortex (dACC), the medial temporal lobe (hippocampus, HPC), the superior parietal cortex (SPC) and the fusiform gyrus (FG). uFC patterns were dynamic in that sub-networks modulated during Early learning (dACC ↔ SPC, dACC ↔ FG, dPFC ↔ HPC) were not identical to those modulated during Late learning (dACC ↔ HPC, dPFC ↔ FG, FG ↔ SPC). Covert consolidation exerts systematic effects, and these results add to emerging evidence for the constructive role of the brain's "resting state" in potentiating action. 10.1016/j.bandc.2017.10.003
    Rest-related consolidation protects the fine detail of new memories. Craig Michael,Dewar Michaela Scientific reports Newly encoded memories are labile and consolidate over time. The importance of sleep in memory consolidation has been well known for almost a decade. However, recent research has shown that awake quiescence, too, can support consolidation: people remember more new memories if they quietly rest after encoding than if they engage in a task. It is not yet known how exactly this rest-related consolidation benefits new memories, and whether it affects the fine detail of new memories. Using a sensitive picture recognition task, we show that awake quiescence aids the fine detail of new memories. Young adults were significantly better at discriminating recently encoded target pictures from similar lure pictures when the initial encoding of target pictures had been followed immediately by 10 minutes of awake quiescence than an unrelated perceptual task. This novel finding indicates that, in addition to influencing how much we remember, our behavioural state during wakeful consolidation determines, at least in part, the level of fine detail of our new memories. Thus, our results suggest that rest-related consolidation protects the fine detail of new memories, allowing us to retain detailed memories. 10.1038/s41598-018-25313-y
    A systematic review of brain functional connectivity patterns involved in episodic and semantic memory. Palacio Nicole,Cardenas Fernando Reviews in the neurosciences The study of functional connectivity and declarative memory has lately been focused on finding biomarkers of neuropsychological diseases. However, little is known about its patterns in healthy brains. Thus, in this systematic review we analyze and integrate the findings of 81 publications regarding functional connectivity (measured by fMRI during both task and resting-state) and semantic and episodic memory in healthy adults. Moreover, we discriminate and analyze the main areas and links found in specific memory phases (encoding, storage or retrieval) based on several criteria, such as time length, depth of processing, rewarding value of the information, vividness and amount or kind of details retrieved. There is a certain degree of overlap between the networks of episodic and semantic memory and between the encoding and retrieval stages. Although several differences are pointed out during the article, this calls to attention the need for further empirical studies that actively compare both types of memory, particularly using other baseline conditions apart from the traditional resting state. Indeed, the active involvement of the default mode network in both declarative memory and resting condition suggests the possibility that during rest there is an on-going memory processing. We find support for the 'attention to memory' hypothesis, the memory differentiation model and the appropriate transfer hypothesis, but some evidence is inconsistent with the traditional hub-and-spoke model. 10.1515/revneuro-2018-0117
    Awake Reactivation of Prior Experiences Consolidates Memories and Biases Cognition. Tambini Arielle,Davachi Lila Trends in cognitive sciences After experiences are encoded into memory, post-encoding reactivation mechanisms have been proposed to mediate long-term memory stabilization and transformation. Spontaneous reactivation of hippocampal representations, together with hippocampal-cortical interactions, are leading candidate mechanisms for promoting systems-level memory strengthening and reorganization. While the replay of spatial representations has been extensively studied in rodents, here we review recent fMRI work that provides evidence for spontaneous reactivation of nonspatial, episodic event representations in the human hippocampus and cortex, as well as for experience-dependent alterations in systems-level hippocampal connectivity. We focus on reactivation during awake post-encoding periods, relationships between reactivation and subsequent behavior, how reactivation is modulated by factors that influence consolidation, and the implications of persistent reactivation for biasing ongoing perception and cognition. 10.1016/j.tics.2019.07.008
    The amygdala modulates the consolidation of memories of emotionally arousing experiences. McGaugh James L Annual review of neuroscience Converging findings of animal and human studies provide compelling evidence that the amygdala is critically involved in enabling us to acquire and retain lasting memories of emotional experiences. This review focuses primarily on the findings of research investigating the role of the amygdala in modulating the consolidation of long-term memories. Considerable evidence from animal studies investigating the effects of posttraining systemic or intra-amygdala infusions of hormones and drugs, as well as selective lesions of specific amygdala nuclei, indicates that (a) the amygdala mediates the memory-modulating effects of adrenal stress hormones and several classes of neurotransmitters; (b) the effects are selectively mediated by the basolateral complex of the amygdala (BLA); (c) the influences involve interactions of several neuromodulatory systems within the BLA that converge in influencing noradrenergic and muscarinic cholinergic activation; (d) the BLA modulates memory consolidation via efferents to other brain regions, including the caudate nucleus, nucleus accumbens, and cortex; and (e) the BLA modulates the consolidation of memory of many different kinds of information. The findings of human brain imaging studies are consistent with those of animal studies in suggesting that activation of the amygdala influences the consolidation of long-term memory; the degree of activation of the amygdala by emotional arousal during encoding of emotionally arousing material (either pleasant or unpleasant) correlates highly with subsequent recall. The activation of neuromodulatory systems affecting the BLA and its projections to other brain regions involved in processing different kinds of information plays a key role in enabling emotionally significant experiences to be well remembered. 10.1146/annurev.neuro.27.070203.144157
    Memory transformation and systems consolidation. Winocur Gordon,Moscovitch Morris Journal of the International Neuropsychological Society : JINS With time and experience, memories undergo a process of reorganization that involves different neuronal networks, known as systems consolidation. The traditional view, as articulated in standard consolidation theory (SCT), is that (episodic and semantic) memories initially depend on the hippocampus, but eventually become consolidated in their original forms in other brain regions. In this study, we review the main principles of SCT and report evidence from the neuropsychological literature that would not be predicted by this theory. By comparison, the evidence supports an alternative account, the transformation hypothesis, whose central premise is that changes in neural representation in systems consolidation are accompanied by corresponding changes in the nature of the memory. According to this view, hippocampally dependent, episodic, or context-specific memories transform into semantic or gist-like versions that are represented in extra-hippocampal structures. To the extent that episodic memories are retained, they will continue to require the hippocampus, but the hippocampus is not needed for the retrieval of semantic memories. The transformation hypothesis emphasizes the dynamic nature of memory, as well as the underlying functional and neural interactions that must be taken into account in a comprehensive theory of memory. 10.1017/S1355617711000683
    [Impact of interleukin-10 and interleukin-28 gene polymorphisms on the development and course of lupus nephritis]. Krasnova T N,Samokhodskaya L M,Ivanitsky L V,Korogodina A D,Borisov E N,Nikiforova N V,Novikov P I,Kamalov A A,Mukhin N A Terapevticheskii arkhiv AIM:To assess the relationship of the carriage of IL-10-1080 G/A and IL-28 rs8099917 C/T polymorphisms to the course of lupus nephritis (LN). SUBJECTS AND METHODS:Ninety-nine patients with systemic lupus erythematosus (SLE), including 68 with LN, were examined. Gene polymorphisms were analyzed using standard molecular genetic techniques. The frequency of the clinical manifestations of LN was analyzed; renal survival (RS) was estimated by the Kaplan-Meier method. RESULTS:Ten-year RS rates were 80 and 86% of the patients with and without the mutant IL-10 allele, respectively (p = 0.78). The 10-year RS was lower (75%) in carriers of the mutant IL-28 rsl2979860 allele than in patients without this mutant allele (83%; p = 0.049) and in those of the mutant IL28 rs8099917 allele than in patients without the above mutant allele (67 and 88%, respectively; p = 0.047). LN patients, carriers of the mutant IL-10-1028 G/A allele, were observed to have higher-grade proteinuria in the presence of nephritic syndrome (mean 6.1 g/l) than those without the mutant allele of this gene (mean 2.9 g/l; p = 0.034). However, the mutant allele carriers responded to treatment better (p = 0.050). The mutant IL-10 and IL-28 alleles were unassociated with the development of rapidly progressive nephritis, the activity of a renal lupus process, and the rate of onset of SLE and LN. CONCLUSION:In the LN patients, the carriage of the mutant IL-10 allele A is associated with a better response to treatment and that of the mutant IL-28 allele is linked to the severe course of the disease. 10.17116/terarkh201587640-44
    Decision-making Increases Episodic Memory via Postencoding Consolidation. Murty Vishnu P,DuBrow Sarah,Davachi Lila Journal of cognitive neuroscience The ability for individuals to actively make decisions engages regions within the mesolimbic system and enhances memory for chosen items. In other behavioral contexts, mesolimbic engagement has been shown to enhance episodic memory by supporting consolidation. However, research has yet to investigate how consolidation may support interactions between decision-making and episodic memory. Across two studies, participants encoded items that were covered by occluder screens and could either actively decide which of two items to uncover or an item was preselected by the experimenter. In Study 1, we show that active decision-making reduces forgetting rates across an immediate and 24-hr memory test, a behavioral marker of consolidation. In Study 2, we use functional neuroimaging to characterize putative neural markers of memory consolidation by measuring interactions between the hippocampus and perirhinal cortex (PRC) during a postencoding period that reexposed participants to elements of the decision-making context without exposing them to memoranda. We show that choice-related striatal engagement is associated with increased postencoding hippocampal-PRC interactions. Finally, we show that a previous reported relationship between choice-related striatal engagement and long-term memory is accounted for by these postencoding hippocampal-PRC interactions. Together, these findings support a model by which actively deciding to encode information enhances memory consolidation to preserve episodic memory for outcomes, a process that may be facilitated by reexposure to the original decision-making context. 10.1162/jocn_a_01321
    Spontaneous cognitive processes and the behavioral validation of time-varying brain connectivity. Kucyi Aaron,Tambini Arielle,Sadaghiani Sepideh,Keilholz Shella,Cohen Jessica R Network neuroscience (Cambridge, Mass.) In cognitive neuroscience, focus is commonly placed on associating brain function with changes in objectively measured external stimuli or with actively generated cognitive processes. In everyday life, however, many forms of cognitive processes are initiated spontaneously, without an individual's active effort and without explicit manipulation of behavioral state. Recently, there has been increased emphasis, especially in functional neuroimaging research, on spontaneous correlated activity among spatially segregated brain regions (intrinsic functional connectivity) and, more specifically, on intraindividual fluctuations of such correlated activity on various time scales (time-varying functional connectivity). In this Perspective, we propose that certain subtypes of spontaneous cognitive processes are detectable in time-varying functional connectivity measurements. We define these subtypes of spontaneous cognitive processes and review evidence of their representations in time-varying functional connectivity from studies of attentional fluctuations, memory reactivation, and effects of baseline states on subsequent perception. Moreover, we describe how these studies are critical to validating the use of neuroimaging tools (e.g., fMRI) for assessing ongoing brain network dynamics. We conclude that continued investigation of the behavioral relevance of time-varying functional connectivity will be beneficial both in the development of comprehensive neural models of cognition, and in informing on best practices for studying brain network dynamics. 10.1162/netn_a_00037
    Age-related emotional bias in associative memory consolidation: The role of sleep. Huan Sheng-Yin,Liu Kun-Peng,Lei Xu,Yu Jing Neurobiology of learning and memory Sleep plays a crucial role in memory consolidation. However, the influence of sleep on emotional memory consolidation in older adults, especially in the context of associative memory, which is more cognitively demanding than item memory, remains elusive. For this study we recruited young and older adults, and randomly assigned them into the sleep or wake condition. They were administrated a visual-spatial associative memory task, which required them to remember a picture and its location. We measured memory performance for positive, neutral, and negative stimuli before and after a 12-h interval of being awake or asleep. An accuracy analysis indicated a beneficial effect of sleep on location memory regardless of age and valence. In addition, in a more fine-grained analysis, the drift rate from diffusion modeling showed that sleep facilitated the consolidation of negative stimuli in young adults, while this emotion bias shifted to positive stimuli in older adults. Moreover, negative correlations were observed between the change of memory performance and sleep characteristics in older adults, indicating that more sleep results in fewer negative memories. Our results provide a relatively weak support for an age-related emotional bias in the context of associative memory, manifested in the absence of an age-by-valence interaction in accuracy, whilst a modeling parameter in consideration of both accuracy and response time yielded evidence consistent with the predictions of the socioemotional selectivity theory. 10.1016/j.nlm.2020.107204
    A Note on an Improved Self-Healing Group Key Distribution Scheme. Guo Hua,Zheng Yandong,Wang Biao,Li Zhoujun Sensors (Basel, Switzerland) In 2014, Chen et al. proposed a one-way hash self-healing group key distribution scheme for resource-constrained wireless networks in the journal of Sensors (14(14):24358-24380, doi: 10.3390/ s141224358). They asserted that their Scheme 2 achieves mt-revocation capability, mt-wise forward secrecy, any-wise backward secrecy and has mt-wise collusion attack resistance capability. Unfortunately, this paper pointed out that their scheme does not satisfy the forward security, mt-revocation capability and mt-wise collusion attack resistance capability. 10.3390/s151025033
    Mnemonic Training Reshapes Brain Networks to Support Superior Memory. Dresler Martin,Shirer William R,Konrad Boris N,Müller Nils C J,Wagner Isabella C,Fernández Guillén,Czisch Michael,Greicius Michael D Neuron Memory skills strongly differ across the general population; however, little is known about the brain characteristics supporting superior memory performance. Here we assess functional brain network organization of 23 of the world's most successful memory athletes and matched controls with fMRI during both task-free resting state baseline and active memory encoding. We demonstrate that, in a group of naive controls, functional connectivity changes induced by 6 weeks of mnemonic training were correlated with the network organization that distinguishes athletes from controls. During rest, this effect was mainly driven by connections between rather than within the visual, medial temporal lobe and default mode networks, whereas during task it was driven by connectivity within these networks. Similarity with memory athlete connectivity patterns predicted memory improvements up to 4 months after training. In conclusion, mnemonic training drives distributed rather than regional changes, reorganizing the brain's functional network organization to enable superior memory performance. 10.1016/j.neuron.2017.02.003
    The effect of prior knowledge on post-encoding brain connectivity and its relation to subsequent memory. Liu Zhong-Xu,Grady Cheryl,Moscovitch Morris NeuroImage It is known that prior knowledge can facilitate memory acquisition. It is unclear, however, whether prior knowledge can affect post-encoding brain activity to facilitate memory consolidation. In this fMRI study, we asked participants to associate novel houses with famous/nonfamous faces and investigated how associative-encoding tasks with/without prior knowledge differentially affected post-encoding brain connectivity during rest. Besides memory advantages in the famous condition, we found that post-encoding hippocampal connectivity with the fusiform face area (FFA) and ventral-medial-prefrontal cortex (vmPFC) was stronger following encoding of associations with famous than non-famous faces. Importantly, post-encoding functional connectivity between the hippocampus (HPC) and FFA, and between the anterior temporal pole region (aTPL) and posterior perceptual regions (i.e., FFA and the parahippocampal place area), together predicted a large proportion of the variance in subsequent memory performance. This prediction was specific for face-house associative memory, not face/house item memory, and only in the famous condition where prior knowledge was involved. These results support the idea that when prior knowledge is involved, the HPC, vmPFC, and aTPL, which support prior episodic, social-evaluative/schematic, and semantic memories, respectively, continue to interact with each other and posterior perceptual brain regions during the post-encoding rest to facilitate off-line processing of the newly formed memory, and enhance memory consolidation. 10.1016/j.neuroimage.2017.11.032
    Hippocampal-targeted Theta-burst Stimulation Enhances Associative Memory Formation. Tambini Arielle,Nee Derek Evan,D'Esposito Mark Journal of cognitive neuroscience The hippocampus plays a critical role in episodic memory, among other cognitive functions. However, few tools exist to causally manipulate hippocampal function in healthy human participants. Recent work has targeted hippocampal-cortical networks by performing TMS to a region interconnected with the hippocampus, posterior inferior parietal cortex (pIPC). Such hippocampal-targeted TMS enhances associative memory and influences hippocampal functional connectivity. However, it is currently unknown which stages of mnemonic processing (encoding or retrieval) are affected by hippocampal-targeted TMS. Here, we examined whether hippocampal-targeted TMS influences the initial encoding of associations (vs. items) into memory. To selectively influence encoding and not retrieval, we performed continuous theta-burst TMS before participants encoded object-location associations and assessed memory after the direct effect of stimulation dissipated. Relative to control TMS and baseline memory, pIPC TMS enhanced associative memory success and confidence. Item memory was unaffected, demonstrating a selective influence on associative versus item memory. The strength of hippocampal-pIPC functional connectivity predicted TMS-related memory benefits, which was mediated by parahippocampal and retrosplenial cortices. Our findings indicate that hippocampal-targeted TMS can specifically modulate the encoding of new associations into memory without directly influencing retrieval processes and suggest that the ability to influence associative memory may be related to the fidelity of hippocampal TMS targeting. These results support the notion that pIPC TMS may serve as a potential tool for manipulating hippocampal function in healthy participants. Nonetheless, future work combining hippocampal-targeted continuous theta-burst TMS with neuroimaging is needed to better understand the neural basis of TMS-induced memory changes. 10.1162/jocn_a_01300
    Effects of Repetition Learning on Associative Recognition Over Time: Role of the Hippocampus and Prefrontal Cortex. Zhan Lexia,Guo Dingrong,Chen Gang,Yang Jiongjiong Frontiers in human neuroscience When stimuli are learned by repetition, they are remembered better and retained for a longer time. However, current findings are lacking as to whether the medial temporal lobe (MTL) and cortical regions are involved in the learning effect when subjects retrieve associative memory, and whether their activations differentially change over time due to learning experience. To address these issues, we designed an fMRI experiment in which face-scene pairs were learned once (L1) or six times (L6). Subjects learned the pairs at four retention intervals, 30-min, 1-day, 1-week and 1-month, after which they finished an associative recognition task in the scanner. The results showed that compared to learning once, learning six times led to stronger activation in the hippocampus, but weaker activation in the perirhinal cortex (PRC) as well as anterior ventrolateral prefrontal cortex (vLPFC). In addition, the hippocampal activation was positively correlated with that of the parahippocampal place area (PPA) and negatively correlated with that of the vLPFC when the L6 group was compared to the L1 group. The hippocampal activation decreased over time after L1 but remained stable after L6. These results clarified how the hippocampus and cortical regions interacted to support associative memory after different learning experiences. 10.3389/fnhum.2018.00277
    Hippocampal signatures of awake targeted memory reactivation. Alm Kylie H,Ngo Chi T,Olson Ingrid R Brain structure & function Dominant theories of episodic memory propose that a key mechanism of memory consolidation is replay-a process, whereby neural patterns of activation during learning are reinstated during offline post-learning periods. Here, we tested whether key signatures of replay defined by studies in rodents, such as recapitulation of specific memory traces, as well as sequences, are apparent in humans during post-encoding memory reactivation. Thirty participants underwent functional imaging that consisted of interleaved encoding and rest periods. During an offline period of wakeful rest, we biased reactivation towards some memories by presenting sound cues that had previously been associated with particular stimulus sequences. Results showed that targeted hippocampal reactivation was biased towards cued memory sequences and that reactivation signatures preserved the temporal order of particular sequences. Importantly, the biased reactivation was related to differences in subsequent memory, suggesting that preferential reactivation may be a mechanism by which specific memory traces can be strengthened for enhanced subsequent memory retrieval. 10.1007/s00429-018-1790-2
    Scenes facilitate associative memory and integration. Robin Jessica,Olsen Rosanna K Learning & memory (Cold Spring Harbor, N.Y.) How do we form mental links between related items? Forming associations between representations is a key feature of episodic memory and provides the foundation for learning and guiding behavior. Theories suggest that spatial context plays a supportive role in episodic memory, providing a scaffold on which to form associations, but this has mostly been tested in the context of autobiographical memory. We examined the memory boosting effect of spatial stimuli in memory using an associative inference paradigm combined with eye-tracking. Across two experiments, we found that memory was better for associations that included scenes, even indirectly, compared to objects and faces. Eye-tracking measures indicated that these effects may be partly mediated by greater fixations to scenes compared to objects, but did not explain the differences between scenes and faces. These results suggest that scenes facilitate associative memory and integration across memories, demonstrating evidence in support of theories of scenes as a spatial scaffold for episodic memory. A shared spatial context may promote learning and could potentially be leveraged to improve learning and memory in educational settings or for memory-impaired populations. 10.1101/lm.049486.119
    Memory consolidation by replay of stimulus-specific neural activity. Deuker Lorena,Olligs Jan,Fell Juergen,Kranz Thorsten A,Mormann Florian,Montag Christian,Reuter Martin,Elger Christian E,Axmacher Nikolai The Journal of neuroscience : the official journal of the Society for Neuroscience Memory consolidation transforms initially labile memory traces into more stable representations. One putative mechanism for consolidation is the reactivation of memory traces after their initial encoding during subsequent sleep or waking state. However, it is still unknown whether consolidation of individual memory contents relies on reactivation of stimulus-specific neural representations in humans. Investigating stimulus-specific representations in humans is particularly difficult, but potentially feasible using multivariate pattern classification analysis (MVPA). Here, we show in healthy human participants that stimulus-specific activation patterns can indeed be identified with MVPA, that these patterns reoccur spontaneously during postlearning resting periods and sleep, and that the frequency of reactivation predicts subsequent memory for individual items. We conducted a paired-associate learning task with items and spatial positions and extracted stimulus-specific activity patterns by MVPA in a simultaneous electroencephalography and functional magnetic resonance imaging (fMRI) study. As a first step, we investigated the amount of fMRI volumes during rest that resembled either one of the items shown before or one of the items shown as a control after the resting period. Reactivations during both awake resting state and sleep predicted subsequent memory. These data are first evidence that spontaneous reactivation of stimulus-specific activity patterns during resting state can be investigated using MVPA. They show that reactivation occurs in humans and is behaviorally relevant for stabilizing memory traces against interference. They move beyond previous studies because replay was investigated on the level of individual stimuli and because reactivations were not evoked by sensory cues but occurred spontaneously. 10.1523/JNEUROSCI.0414-13.2013
    Memory consolidation. Squire Larry R,Genzel Lisa,Wixted John T,Morris Richard G Cold Spring Harbor perspectives in biology Conscious memory for a new experience is initially dependent on information stored in both the hippocampus and neocortex. Systems consolidation is the process by which the hippocampus guides the reorganization of the information stored in the neocortex such that it eventually becomes independent of the hippocampus. Early evidence for systems consolidation was provided by studies of retrograde amnesia, which found that damage to the hippocampus-impaired memories formed in the recent past, but typically spared memories formed in the more remote past. Systems consolidation has been found to occur for both episodic and semantic memories and for both spatial and nonspatial memories, although empirical inconsistencies and theoretical disagreements remain about these issues. Recent work has begun to characterize the neural mechanisms that underlie the dialogue between the hippocampus and neocortex (e.g., "neural replay," which occurs during sharp wave ripple activity). New work has also identified variables, such as the amount of preexisting knowledge, that affect the rate of consolidation. The increasing use of molecular genetic tools (e.g., optogenetics) can be expected to further improve understanding of the neural mechanisms underlying consolidation. 10.1101/cshperspect.a021766
    Post-learning Hippocampal Dynamics Promote Preferential Retention of Rewarding Events. Gruber Matthias J,Ritchey Maureen,Wang Shao-Fang,Doss Manoj K,Ranganath Charan Neuron Reward motivation is known to modulate memory encoding, and this effect depends on interactions between the substantia nigra/ventral tegmental area complex (SN/VTA) and the hippocampus. It is unknown, however, whether these interactions influence offline neural activity in the human brain that is thought to promote memory consolidation. Here we used fMRI to test the effect of reward motivation on post-learning neural dynamics and subsequent memory for objects that were learned in high- and low-reward motivation contexts. We found that post-learning increases in resting-state functional connectivity between the SN/VTA and hippocampus predicted preferential retention of objects that were learned in high-reward contexts. In addition, multivariate pattern classification revealed that hippocampal representations of high-reward contexts were preferentially reactivated during post-learning rest, and the number of hippocampal reactivations was predictive of preferential retention of items learned in high-reward contexts. These findings indicate that reward motivation alters offline post-learning dynamics between the SN/VTA and hippocampus, providing novel evidence for a potential mechanism by which reward could influence memory consolidation. 10.1016/j.neuron.2016.01.017
    Brief wakeful resting can eliminate directed forgetting. Schlichting Andreas,Bäuml Karl-Heinz T Memory (Hove, England) When cued to intentionally forget previously encoded memories, participants typically show reduced recall of the memories on a later recall test. We examined how such directed forgetting is affected by a brief period of wakeful resting between encoding and test. Encoding was followed by a "passive" wakeful resting period in which subjects heard emotionally neutral music or perceived neutral pictures, or it was followed by an "active" distraction period in which subjects were engaged in counting or calculation tasks. Whereas typical directed forgetting was present after active distraction, the forgetting was absent after wakeful resting. The findings indicate that the degree to which people can intentionally forget memories is influenced by the cognitive activity that people engage in shortly after learning takes place. The results provide first evidence on the interplay between wakeful resting and intentional forgetting. 10.1080/09658211.2016.1153659
    High-resolution investigation of memory-specific reinstatement in the hippocampus and perirhinal cortex. Tompary Alexa,Duncan Katherine,Davachi Lila Hippocampus Episodic memory involves remembering the details that characterize a prior experience. Successful memory recovery has been associated with the reinstatement of brain activity patterns in a number of sensory regions across the cortex. However, how the hippocampus and surrounding medial temporal lobe (MTL) cortex contribute to this process is less clear. Models of episodic memory posit that hippocampal pattern reinstatement, also referred to as pattern completion, may mediate cortical reinstatement during retrieval. Empirical evidence of this process, however, remains elusive. Here, we use high-resolution fMRI and encoding-retrieval multi-voxel pattern similarity analyses to demonstrate for the first time that the hippocampus, particularly right hippocampal subfield CA1, shows evidence of reinstating individual episodic memories. Furthermore, reinstatement in perirhinal cortex (PrC) is also evident. Critically, we identify distinct factors that may mediate the cortical reinstatement in PrC. First, we find that encoding activation in PrC is related to later reinstatement in this region, consistent with the theory that encoding strength in the regions that process the memoranda is important for later reinstatement. Conversely, retrieval activation in right CA1 was correlated with reinstatement in PrC, consistent with models of pattern completion. This dissociation is discussed in the context of the flow of information into and out of the hippocampus during encoding and retrieval, respectively. © 2016 Wiley Periodicals, Inc. 10.1002/hipo.22582
    Awake, Offline Processing during Associative Learning. Bursley James K,Nestor Adrian,Tarr Michael J,Creswell J David PloS one Offline processing has been shown to strengthen memory traces and enhance learning in the absence of conscious rehearsal or awareness. Here we evaluate whether a brief, two-minute offline processing period can boost associative learning and test a memory reactivation account for these offline processing effects. After encoding paired associates, subjects either completed a distractor task for two minutes or were immediately tested for memory of the pairs in a counterbalanced, within-subjects functional magnetic resonance imaging study. Results showed that brief, awake, offline processing improves memory for associate pairs. Moreover, multi-voxel pattern analysis of the neuroimaging data suggested reactivation of encoded memory representations in dorsolateral prefrontal cortex during offline processing. These results signify the first demonstration of awake, active, offline enhancement of associative memory and suggest that such enhancement is accompanied by the offline reactivation of encoded memory representations. 10.1371/journal.pone.0127522
    Hippocampo-cortical coupling mediates memory consolidation during sleep. Maingret Nicolas,Girardeau Gabrielle,Todorova Ralitsa,Goutierre Marie,Zugaro Michaël Nature neuroscience Memory consolidation is thought to involve a hippocampo-cortical dialog during sleep to stabilize labile memory traces for long-term storage. However, direct evidence supporting this hypothesis is lacking. We dynamically manipulated the temporal coordination between the two structures during sleep following training on a spatial memory task specifically designed to trigger encoding, but not memory consolidation. Reinforcing the endogenous coordination between hippocampal sharp wave-ripples, cortical delta waves and spindles by timed electrical stimulation resulted in a reorganization of prefrontal cortical networks, along with subsequent increased prefrontal responsivity to the task and high recall performance on the next day, contrary to control rats, which performed at chance levels. Our results provide, to the best of our knowledge, the first direct evidence for a causal role of a hippocampo-cortical dialog during sleep in memory consolidation, and indicate that the underlying mechanism involves a fine-tuned coordination between sharp wave-ripples, delta waves and spindles. 10.1038/nn.4304
    Consolidation Promotes the Emergence of Representational Overlap in the Hippocampus and Medial Prefrontal Cortex. Tompary Alexa,Davachi Lila Neuron Structured knowledge is thought to form, in part, through the extraction and representation of regularities across overlapping experiences. However, little is known about how consolidation processes may transform novel episodic memories to reflect such regularities. In a multi-day fMRI study, participants encoded trial-unique associations that shared features with other trials. Multi-variate pattern analyses were used to measure neural similarity across overlapping and non-overlapping memories during immediate and 1-week retrieval of these associations. We found that neural patterns in the hippocampus and medial prefrontal cortex represented the featural overlap across memories, but only after a week. Furthermore, after a week, the strength of a memory's unique episodic reinstatement during retrieval was inversely related to its representation of overlap, suggesting a trade-off between the integration of related memories and recovery of episodic details. These findings suggest that consolidation-related changes in neural representations support the gradual organization of discrete episodes into structured knowledge. 10.1016/j.neuron.2017.09.005
    Human hippocampal replay during rest prioritizes weakly learned information and predicts memory performance. Schapiro Anna C,McDevitt Elizabeth A,Rogers Timothy T,Mednick Sara C,Norman Kenneth A Nature communications The hippocampus replays experiences during quiet rest periods, and this replay benefits subsequent memory. A critical open question is how memories are prioritized for this replay. We used functional magnetic resonance imaging (fMRI) pattern analysis to track item-level replay in the hippocampus during an awake rest period after participants studied 15 objects and completed a memory test. Objects that were remembered less well were replayed more during the subsequent rest period, suggesting a prioritization process in which weaker memories-memories most vulnerable to forgetting-are selected for replay. In a second session 12 hours later, more replay of an object during a rest period predicted better subsequent memory for that object. Replay predicted memory improvement across sessions only for participants who slept during that interval. Our results provide evidence that replay in the human hippocampus prioritizes weakly learned information, predicts subsequent memory performance, and relates to memory improvement across a delay with sleep. 10.1038/s41467-018-06213-1
    International authorship and collaboration across bioRxiv preprints. Abdill Richard J,Adamowicz Elizabeth M,Blekhman Ran eLife Preprints are becoming well established in the life sciences, but relatively little is known about the demographics of the researchers who post preprints and those who do not, or about the collaborations between preprint authors. Here, based on an analysis of 67,885 preprints posted on bioRxiv, we find that some countries, notably the United States and the United Kingdom, are overrepresented on bioRxiv relative to their overall scientific output, while other countries (including China, Russia, and Turkey) show lower levels of bioRxiv adoption. We also describe a set of 'contributor countries' (including Uganda, Croatia and Thailand): researchers from these countries appear almost exclusively as non-senior authors on international collaborations. Lastly, we find multiple journals that publish a disproportionate number of preprints from some countries, a dynamic that almost always benefits manuscripts from the US. 10.7554/eLife.58496
    Increased Serum Level of Interleukin-10 Predicts Poor Survival and Early Recurrence in Patients With Peripheral T-Cell Lymphomas. Zhang Yan,Zheng Yanlong,Shou Lihong,Shi Yuanfei,Shen Huafei,Zhu Mingyu,Ye Xiujin,Jin Jie,Xie Wanzhuo Frontiers in oncology Peripheral T cell lymphoma (PTCL) is an alloplasm group of aggressive and lymphoproliferative tumors with heterogeneous morphological changes of mature T cell immunophenotype. It has multiple subtypes and most of them have poor prognosis. Interleukin 10 (IL-10) is one kind of multi-cell-derived and multifunctional cytokine. It regulates the growth and differentiation of cells, participates in inflammation and immune response, plays an important role in tumor and infection, and is closely related to blood system diseases. Therefore, we implemented a retrospective study of 205 patients who were newly diagnosed with PTCL to explore the relationship between IL-10 and prognosis and early recurrence. We found patients with IL-10 ≥3.6 pg/ml achieved a lower CR rate and higher 1-year recurrence rate than patients with IL-10 <3.6 pg/ml (14.4 vs. 51.9%; 17.6 vs. 49.5%). On multivariate analysis, moreover, elevated IL-10 is an extremely important prognostic factor in PTCL, which can lead to worsening of overall survival (OS), low complete response (CR) rate and higher early relapse rate. Therefore, measurement of IL-10 levels in peripheral blood at the initial stage are useful for predicting the prognosis and helping us to make different treatment plans for individual patients. In the near future, IL-10 inhibitors or antagonists may become a new method of immunotargeting therapy for patients with PTCL. 10.3389/fonc.2020.584261
    Awake suppression after brief exposure to a familiar stimulus. Bang Ji Won,Rahnev Dobromir Communications biology Newly learned information undergoes a process of awake reactivation shortly after the learning offset and we recently demonstrated that this effect can be observed as early as area V1. However, reactivating all experiences can be wasteful and unnecessary, especially for familiar stimuli. Therefore, here we tested whether awake reactivation occurs differentially for new and familiar stimuli. Subjects completed a brief visual task on a stimulus that was either novel or highly familiar due to extensive prior training on it. Replicating our previous results, we found that awake reactivation occurred in V1 for the novel stimulus. On the other hand, brief exposure to the familiar stimulus led to 'awake suppression' such that neural activity patterns immediately after exposure to the familiar stimulus diverged from the patterns associated with that stimulus. Further, awake reactivation was observed selectively in V1, whereas awake suppression had similar strength across areas V1-V3. These results are consistent with the presence of a competition between local awake reactivation and top-down awake suppression, with suppression becoming dominant for familiar stimuli. 10.1038/s42003-021-01863-2
    Multiple routes to memory: distinct medial temporal lobe processes build item and source memories. Davachi Lila,Mitchell Jason P,Wagner Anthony D Proceedings of the National Academy of Sciences of the United States of America A central function of memory is to permit an organism to distinguish between stimuli that have been previously encountered and those that are novel. Although the medial temporal lobe (which includes the hippocampus and surrounding perirhinal, parahippocampal, and entorhinal cortices) is known to be crucial for recognition memory, controversy remains regarding how the specific subregions within the medial temporal lobe contribute to recognition. We used event-related functional MRI to examine the relation between activation in distinct medial temporal lobe subregions during memory formation and the ability (i) to later recognize an item as previously encountered (item recognition) and (ii) to later recollect specific contextual details about the prior encounter (source recollection). Encoding activation in hippocampus and in posterior parahippocampal cortex predicted later source recollection, but was uncorrelated with item recognition. In contrast, encoding activation in perirhinal cortex predicted later item recognition, but not subsequent source recollection. These outcomes suggest that the subregions within the medial temporal lobe subserve distinct, but complementary, learning mechanisms. 10.1073/pnas.0337195100
    Selective and shared contributions of the hippocampus and perirhinal cortex to episodic item and associative encoding. Staresina Bernhard P,Davachi Lila Journal of cognitive neuroscience Although the general role of the medial-temporal lobe (MTL) in episodic memory is well established, controversy surrounds the precise division of labor between distinct MTL subregions. The perirhinal cortex (PrC) has been hypothesized to support nonassociative item encoding that contributes to later familiarity, whereas the hippocampus supports associative encoding that selectively contributes to later recollection. However, because previous paradigms have predominantly used recollection of the item context as a measure of associative encoding, it remains unclear whether recollection of different kinds of episodic detail depends on the same or different MTL encoding operations. In our current functional magnetic resonance imaging study, we devised a subsequent memory paradigm that assessed successful item encoding in addition to the encoding of two distinct episodic details: an item-color and an item-context detail. Hippocampal encoding activation was selectively enhanced during trials leading to successful recovery of either an item-color or item-context association. Moreover, the magnitude of hippocampal activation correlated with the number, and not the kind, of associated details successfully bound, providing strong evidence for a role of the hippocampus in domain-general associative encoding. By contrast, PrC encoding activation correlated with both nonassociative item encoding as well as associative item-color binding, but not with item-context binding. This pattern suggests that the PrC contributions to memory encoding may be domain-specific and limited to the binding of items with presented item-related features. Critically, together with a separately conducted behavioral study, these data raise the possibility that PrC encoding operations -- in conjunction with hippocampal mechanisms -- contribute to later recollection of presented item details. 10.1162/jocn.2008.20104
    The memory function of sleep. Diekelmann Susanne,Born Jan Nature reviews. Neuroscience Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory, depending on the specific conditions of learning and the timing of sleep. Consolidation during sleep promotes both quantitative and qualitative changes of memory representations. Through specific patterns of neuromodulatory activity and electric field potential oscillations, slow-wave sleep (SWS) and rapid eye movement (REM) sleep support system consolidation and synaptic consolidation, respectively. During SWS, slow oscillations, spindles and ripples - at minimum cholinergic activity - coordinate the re-activation and redistribution of hippocampus-dependent memories to neocortical sites, whereas during REM sleep, local increases in plasticity-related immediate-early gene activity - at high cholinergic and theta activity - might favour the subsequent synaptic consolidation of memories in the cortex. 10.1038/nrn2762
    Hippocampal replay in the awake state: a potential substrate for memory consolidation and retrieval. Carr Margaret F,Jadhav Shantanu P,Frank Loren M Nature neuroscience The hippocampus is required for the encoding, consolidation and retrieval of event memories. Although the neural mechanisms that underlie these processes are only partially understood, a series of recent papers point to awake memory replay as a potential contributor to both consolidation and retrieval. Replay is the sequential reactivation of hippocampal place cells that represent previously experienced behavioral trajectories and occurs frequently in the awake state, particularly during periods of relative immobility. Awake replay may reflect trajectories through either the current environment or previously visited environments that are spatially remote. The repetition of learned sequences on a compressed time scale is well suited to promote memory consolidation in distributed circuits beyond the hippocampus, suggesting that consolidation occurs in both the awake and sleeping animal. Moreover, sensory information can influence the content of awake replay, suggesting a role for awake replay in memory retrieval. 10.1038/nn.2732
    Perirhinal and parahippocampal cortices differentially contribute to later recollection of object- and scene-related event details. Staresina Bernhard P,Duncan Katherine D,Davachi Lila The Journal of neuroscience : the official journal of the Society for Neuroscience How the different elements of our experiences are encoded into episodic memories has remained one of the major questions in memory research. Although the pivotal role of the medial temporal lobe as a whole for memory formation is well established, much controversy surrounds the precise contributions of the subregions in the medial temporal lobe cortex (MTLC), most notably the perirhinal cortex (PrC) and the parahippocampal cortex (PhC). Although one prominent view links PrC processes with familiarity-based memory and PhC with recollection, an alternative organizing principle is the representational domain critical for successful memory performance (e.g., object- versus scene-related information). In this functional magnetic resonance imaging study, we directly compared successful source encoding during object versus scene imagery, holding perceptual input constant across the two representational domains. Although the hippocampus contributed to associative encoding of both object and scene information, our results revealed a clear double dissociation between PrC and PhC for object- versus scene-related source encoding. In particular, PrC, but not PhC, encoding activation predicted later source memory for the object imagery task, whereas PhC, but not PrC, encoding activation predicted later source memory for the scene imagery task. Interestingly, the transitional zone between PrC and posterior PhC contributed to both object and scene source encoding, possibly reflecting a gradient in domain preference along MTLC. In sum, these results strongly point to representational domain as a key factor determining the involvement of different MTLC subregions during successful episodic memory formation. 10.1523/JNEUROSCI.4978-10.2011
    Brief wakeful resting boosts new memories over the long term. Dewar Michaela,Alber Jessica,Butler Christopher,Cowan Nelson,Della Sala Sergio Psychological science A brief wakeful rest after new verbal learning enhances memory for several minutes. In the research reported here, we explored the possibility of extending this rest-induced memory enhancement over much longer periods. Participants were presented with two stories; one story was followed by a 10-min period of wakeful resting, and the other was followed by a 10-min period during which participants played a spot-the-difference game. In Experiment 1, wakeful resting led to significant enhancement of memory after a 15- to 30-min period and also after 7 days. In experiment 2, this striking enhancement of memory 7 days after learning was demonstrated even when no retrievals were imposed in the interim. The degree to which people can remember prose after 7 days is significantly affected by the cognitive activity that they engage in shortly after new learning takes place. We propose that wakeful resting after new learning allows new memory traces to be consolidated better and hence to be retained for much longer. 10.1177/0956797612441220
    Associative encoding and retrieval are predicted by functional connectivity in distinct hippocampal area CA1 pathways. Duncan Katherine,Tompary Alexa,Davachi Lila The Journal of neuroscience : the official journal of the Society for Neuroscience Determining how the hippocampus supports the unique demands of memory encoding and retrieval is fundamental for understanding the biological basis of episodic memory. One possibility proposed by theoretical models is that the distinct computational demands of encoding and retrieval are accommodated by shifts in the functional interaction between the hippocampal CA1 subregion and its input structures. However, empirical tests of this hypothesis are lacking. To test this in humans, we used high-resolution fMRI to measure functional connectivity between hippocampal area CA1 and regions of the medial temporal lobe and midbrain during extended blocks of associative encoding and retrieval tasks. We found evidence for a double dissociation between the pathways supporting successful encoding and retrieval. Specifically, during the associative encoding task, but not the retrieval task, functional connectivity only between area CA1 and the ventral tegmental area predicted associative long-term memory. In contrast, connectivity between area CA1 and DG/CA3 was greater, on average, during the retrieval task compared with the encoding task, and, importantly, the strength of this connectivity significantly correlated with retrieval success. Together, these findings serve as an important first step toward understanding how the demands of fundamental memory processes may be met by changes in the relative strength of connectivity within hippocampal pathways. 10.1523/JNEUROSCI.0521-14.2014
    Boosting long-term memory via wakeful rest: intentional rehearsal is not necessary, consolidation is sufficient. Dewar Michaela,Alber Jessica,Cowan Nelson,Della Sala Sergio PloS one People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as 'foreign names in a bridge club abroad' and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is not dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is sufficient for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition. 10.1371/journal.pone.0109542
    Post-encoding wakeful resting supports the retention of new verbal memories in children aged 13-14 years. Martini Markus,Martini Caroline,Bernegger Christina,Sachse Pierre The British journal of developmental psychology Evidence primarily exists in adults that engaging in task-related mental activity after new learning results in increased forgetting of learned information, compared with quietly resting in the minutes that follow learning, where less forgetting is observed. The current study investigated whether the beneficial effect of post-encoding rest can be observed in children aged 13-14 years. Each child (N = 102) encoded two word lists. After the presentation and immediate recall of one word list, children wakefully rested for 10 min (resting condition), after presentation and immediate recall of the other word list, they solved visuo-spatial problems for 10 min (problem-solving condition). Seven days later, a surprise free recall test for the two word lists took place. Our results showed that children retained more words over 7 days in the resting condition than with the problem-solving condition. Post-hoc analyses revealed that the resting effect was a function of the number of words recollected during the immediate recall. Specifically, those children who recalled fewest words (≤ 13/30 words) in the immediate recall showed a significant resting effect. There was no resting effect in those who recalled a mid-range (14-16/30 words) or a high number (>16/30 words) of words. These results provide new insights into the factors that influence memory in children, and suggest that a few minutes of wakeful rest benefits memory, relative to engaging in an ongoing task. Statement of contribution What is already known on this subject? Task-related mental activity after encoding weakens memory retention more than wakeful resting. Beneficial effect of resting after encoding was found primarily in younger and older adults. What does this study add? We investigated children at the age of 13-14 years. 8-min post-encoding wakeful resting supports memory retention over 7 days. Individuals differ in the impact of a brief period of wakeful resting after learning. Only children with lower immediate memory performances profited from wakeful resting. 10.1111/bjdp.12267
    Memory Consolidation during Waking Rest. Wamsley Erin J Trends in cognitive sciences Recent studies show that brief periods of rest after learning facilitate consolidation of new memories. This effect is associated with memory-related brain activity during quiet rest and suggests that in our daily lives, moments of unoccupied rest may serve an essential cognitive function. 10.1016/j.tics.2018.12.007
    System consolidation of memory during sleep. Born Jan,Wilhelm Ines Psychological research Over the past two decades, research has accumulated compelling evidence that sleep supports the formation of long-term memory. The standard two-stage memory model that has been originally elaborated for declarative memory assumes that new memories are transiently encoded into a temporary store (represented by the hippocampus in the declarative memory system) before they are gradually transferred into a long-term store (mainly represented by the neocortex), or are forgotten. Based on this model, we propose that sleep, as an offline mode of brain processing, serves the 'active system consolidation' of memory, i.e. the process in which newly encoded memory representations become redistributed to other neuron networks serving as long-term store. System consolidation takes place during slow-wave sleep (SWS) rather than rapid eye movement (REM) sleep. The concept of active system consolidation during sleep implicates that (a) memories are reactivated during sleep to be consolidated, (b) the consolidation process during sleep is selective inasmuch as it does not enhance every memory, and (c) memories, when transferred to the long-term store undergo qualitative changes. Experimental evidence for these three central implications is provided: It has been shown that reactivation of memories during SWS plays a causal role for consolidation, that sleep and specifically SWS consolidates preferentially memories with relevance for future plans, and that sleep produces qualitative changes in memory representations such that the extraction of explicit and conscious knowledge from implicitly learned materials is facilitated. 10.1007/s00426-011-0335-6
    Hippocampal binding of novel information with dominant memory traces can support both memory stability and change. Bridge Donna J,Voss Joel L The Journal of neuroscience : the official journal of the Society for Neuroscience Memory stability and change are considered opposite outcomes. We tested the counterintuitive notion that both depend on one process: hippocampal binding of memory features to associatively novel information, or associative novelty binding (ANB). Building on the idea that dominant memory features, or "traces," are most susceptible to modification, we hypothesized that ANB would selectively involve dominant traces. Therefore, memory stability versus change should depend on whether the currently dominant trace is old versus updated; in either case, novel information will be bound with it, causing either maintenance (when old) or change (when updated). People in our experiment studied objects at locations within scenes (contexts). During reactivation in a new context, subjects moved studied objects to new locations either via active location recall or by passively dragging objects to predetermined locations. After active reactivation, the new object location became dominant in memory, whereas after passive reactivation, the old object location maintained dominance. In both cases, hippocampal ANB bound the currently dominant object-location memory with a context with which it was not paired previously (i.e., associatively novel). Stability occurred in the passive condition when ANB united the dominant original location trace with an associatively novel newer context. Change occurred in the active condition when ANB united the dominant updated object location with an associatively novel and older context. Hippocampal ANB of the currently dominant trace with associatively novel contextual information thus provides a single mechanism to support memory stability and change, with shifts in trace dominance during reactivation dictating the outcome. 10.1523/JNEUROSCI.3819-13.2014
    In search of a recognition memory engram. Brown M W,Banks P J Neuroscience and biobehavioral reviews A large body of data from human and animal studies using psychological, recording, imaging, and lesion techniques indicates that recognition memory involves at least two separable processes: familiarity discrimination and recollection. Familiarity discrimination for individual visual stimuli seems to be effected by a system centred on the perirhinal cortex of the temporal lobe. The fundamental change that encodes prior occurrence within the perirhinal cortex is a reduction in the responses of neurones when a stimulus is repeated. Neuronal network modelling indicates that a system based on such a change in responsiveness is potentially highly efficient in information theoretic terms. A review is given of findings indicating that perirhinal cortex acts as a storage site for recognition memory of objects and that such storage depends upon processes producing synaptic weakening. 10.1016/j.neubiorev.2014.09.016
    The Consolidation and Transformation of Memory. Dudai Yadin,Karni Avi,Born Jan Neuron Memory consolidation refers to the transformation over time of experience-dependent internal representations and their neurobiological underpinnings. The process is assumed to be embodied in synaptic and cellular modifications at brain circuits in which the memory is initially encoded and to proceed by recurrent reactivations, both during wakefulness and during sleep, culminating in the distribution of information to additional locales and integration of new information into existing knowledge. We present snapshots of our current knowledge and gaps in knowledge concerning the progress of consolidation over time and the cognitive architecture that supports it and shapes our long-term memories. 10.1016/j.neuron.2015.09.004
    Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation. Moscovitch Morris,Cabeza Roberto,Winocur Gordon,Nadel Lynn Annual review of psychology The last decade has seen dramatic technological and conceptual changes in research on episodic memory and the brain. New technologies, and increased use of more naturalistic observations, have enabled investigators to delve deeply into the structures that mediate episodic memory, particularly the hippocampus, and to track functional and structural interactions among brain regions that support it. Conceptually, episodic memory is increasingly being viewed as subject to lifelong transformations that are reflected in the neural substrates that mediate it. In keeping with this dynamic perspective, research on episodic memory (and the hippocampus) has infiltrated domains, from perception to language and from empathy to problem solving, that were once considered outside its boundaries. Using the component process model as a framework, and focusing on the hippocampus, its subfields, and specialization along its longitudinal axis, along with its interaction with other brain regions, we consider these new developments and their implications for the organization of episodic memory and its contribution to functions in other domains. 10.1146/annurev-psych-113011-143733
    Resting state fMRI: A review on methods in resting state connectivity analysis and resting state networks. Smitha K A,Akhil Raja K,Arun K M,Rajesh P G,Thomas Bejoy,Kapilamoorthy T R,Kesavadas Chandrasekharan The neuroradiology journal The inquisitiveness about what happens in the brain has been there since the beginning of humankind. Functional magnetic resonance imaging is a prominent tool which helps in the non-invasive examination, localisation as well as lateralisation of brain functions such as language, memory, etc. In recent years, there is an apparent shift in the focus of neuroscience research to studies dealing with a brain at 'resting state'. Here the spotlight is on the intrinsic activity within the brain, in the absence of any sensory or cognitive stimulus. The analyses of functional brain connectivity in the state of rest have revealed different resting state networks, which depict specific functions and varied spatial topology. However, different statistical methods have been introduced to study resting state functional magnetic resonance imaging connectivity, yet producing consistent results. In this article, we introduce the concept of resting state functional magnetic resonance imaging in detail, then discuss three most widely used methods for analysis, describe a few of the resting state networks featuring the brain regions, associated cognitive functions and clinical applications of resting state functional magnetic resonance imaging. This review aims to highlight the utility and importance of studying resting state functional magnetic resonance imaging connectivity, underlining its complementary nature to the task-based functional magnetic resonance imaging. 10.1177/1971400917697342
    A contextual binding theory of episodic memory: systems consolidation reconsidered. Yonelinas Andrew P,Ranganath Charan,Ekstrom Arne D,Wiltgen Brian J Nature reviews. Neuroscience Episodic memory reflects the ability to recollect the temporal and spatial context of past experiences. Episodic memories depend on the hippocampus but have been proposed to undergo rapid forgetting unless consolidated during offline periods such as sleep to neocortical areas for long-term storage. Here, we propose an alternative to this standard systems consolidation theory (SSCT) - a contextual binding account - in which the hippocampus binds item-related and context-related information. We compare these accounts in light of behavioural, lesion, neuroimaging and sleep studies of episodic memory and contend that forgetting is largely due to contextual interference, episodic memory remains dependent on the hippocampus across time, contextual drift produces post-encoding activity and sleep benefits memory by reducing contextual interference. 10.1038/s41583-019-0150-4
    Mechanisms of systems memory consolidation during sleep. Klinzing Jens G,Niethard Niels,Born Jan Nature neuroscience Long-term memory formation is a major function of sleep. Based on evidence from neurophysiological and behavioral studies mainly in humans and rodents, we consider the formation of long-term memory during sleep as an active systems consolidation process that is embedded in a process of global synaptic downscaling. Repeated neuronal replay of representations originating from the hippocampus during slow-wave sleep leads to a gradual transformation and integration of representations in neocortical networks. We highlight three features of this process: (i) hippocampal replay that, by capturing episodic memory aspects, drives consolidation of both hippocampus-dependent and non-hippocampus-dependent memory; (ii) brain oscillations hallmarking slow-wave and rapid-eye movement sleep that provide mechanisms for regulating both information flow across distant brain networks and local synaptic plasticity; and (iii) qualitative transformations of memories during systems consolidation resulting in abstracted, gist-like representations. 10.1038/s41593-019-0467-3
    From Knowing to Remembering: The Semantic-Episodic Distinction. Renoult Louis,Irish Muireann,Moscovitch Morris,Rugg Michael D Trends in cognitive sciences The distinction between episodic and semantic memory was first proposed in 1972 by Endel Tulving and is still of central importance in cognitive neuroscience. However, data obtained over the past 30 years or so support the idea that the frontiers between perception and knowledge and between episodic and semantic memory are not as clear cut as previously thought, prompting a rethink of the episodic-semantic distinction. Here, we review recent research on episodic and semantic memory, highlighting similarities between the two systems. Taken together, current behavioral, neuropsychological, and neuroimaging data are compatible with the idea that episodic and semantic memory are inextricably intertwined, yet retain a measure of distinctiveness, despite the fact that their neural correlates demonstrate considerable overlap. 10.1016/j.tics.2019.09.008
    Spontaneous Entry into an "Offline" State during Wakefulness: A Mechanism of Memory Consolidation? Wamsley Erin J,Summer Theodore Journal of cognitive neuroscience Moments of inattention to our surroundings may be essential to optimal cognitive functioning. Here, we investigated the hypothesis that humans spontaneously switch between two opposing attentional states during wakefulness-one in which we attend to the external environment (an "online" state) and one in which we disengage from the sensory environment to focus our attention internally (an "offline" state). We created a data-driven model of this proposed alternation between "online" and "offline" attentional states in humans, on a seconds-level timescale. Participants ( = 34) completed a sustained attention to response task while undergoing simultaneous high-density EEG and pupillometry recording and intermittently reporting on their subjective experience. "Online" and "offline" attentional states were initially defined using a cluster analysis applied to multimodal measures of (1) EEG spectral power, (2) pupil diameter, (3) RT, and (4) self-reported subjective experience. We then developed a classifier that labeled trials as belonging to the online or offline cluster with >95% accuracy, without requiring subjective experience data. This allowed us to classify all 5-sec trials in this manner, despite the fact that subjective experience was probed on only a small minority of trials. We report evidence of statistically discriminable "online" and "offline" states matching the hypothesized characteristics. Furthermore, the offline state strongly predicted memory retention for one of two verbal learning tasks encoded immediately prior. Together, these observations suggest that seconds-timescale alternation between online and offline states is a fundamental feature of wakefulness and that this may serve a memory processing function. 10.1162/jocn_a_01587
    Correction to Lancet Infectious Diseases 2020; published online April 29. https://doi.org/10.1016/ S1473-3099(20)30064-5. The Lancet. Infectious diseases 10.1016/S1473-3099(20)30370-4
    Causal Contribution of Awake Post-encoding Processes to Episodic Memory Consolidation. Tambini Arielle,D'Esposito Mark Current biology : CB Stable representations of past experience are thought to depend on processes that unfold after events are initially encoded into memory. Post-encoding reactivation and hippocampal-cortical interactions are leading candidate mechanisms thought to support memory retention and stabilization across hippocampal-cortical networks. Although putative consolidation mechanisms have been observed during sleep and periods of awake rest, the direct causal contribution of awake consolidation mechanisms to later behavior is unclear, especially in humans. Moreover, it has been argued that observations of putative consolidation processes are epiphenomenal and not causally important, yet there are few tools to test the functional contribution of these mechanisms in humans. Here, we combined transcranial magnetic stimulation (TMS) and fMRI to test the role of awake consolidation processes by targeting hippocampal interactions with lateral occipital cortex (LOC). We applied theta-burst TMS to LOC (and a control site) to interfere with an extended window (approximately 30-50 min) after memory encoding. Behaviorally, post-encoding TMS to LOC selectively impaired associative memory retention compared to multiple control conditions. In the control TMS condition, we replicated prior reports of post-encoding reactivation and memory-related hippocampal-LOC interactions during periods of awake rest using fMRI. However, post-encoding LOC TMS reduced these processes, such that post-encoding reactivation in LOC and memory-related hippocampal-LOC functional connectivity were no longer present. By targeting and manipulating post-encoding neural processes, these findings highlight the direct contribution of awake time periods to episodic memory consolidation. This combined TMS-fMRI approach provides an opportunity for causal manipulations of human memory consolidation. 10.1016/j.cub.2020.06.063
    Complex associative memory processing and sleep: a systematic review and meta-analysis of behavioural evidence and underlying EEG mechanisms. Chatburn Alex,Lushington Kurt,Kohler Mark J Neuroscience and biobehavioral reviews The beneficial influence of sleep on memory consolidation is well established; however, the mechanisms by which sleep can dynamically consolidate new memories into existing networks for the continued environmental adaptation of the individual are unclear. The role of sleep in complex associative memory is an emerging field and the literature has not yet been systematically reviewed. Here, we systematically review the published literature on the role of sleep in complex associative memory processing to determine (i) if there is reasonable published evidence to support an active role for sleep facilitating complex associative processes such rule and gist extraction and false memory; (ii) to determine which sleep physiological events and states impact these processes, and to quantify the strength of these relationships through meta-analysis. Twenty-seven studies in healthy adults were identified which combined indicate a moderate effect of sleep in facilitating associative memory as tested behaviourally. Studies which have measured sleep physiology have reported mixed findings. Significant associations between sleep electrophysiology and outcome appear to be based largely on mode of acquisition. We interpret these findings as supporting reactivation based models of associative processing. 10.1016/j.neubiorev.2014.10.018